Customized Antibiotic Treatment Duration Among Hospitalized Patients With Moderately Severe Community-Acquired Pneumonia
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 328
- 试验地点
- 1
- 主要终点
- Rate of cure at Day 15 after treatment initiation
研究概览
简要总结
The primary objective of the study is to evaluate if the efficacy of an experimental strategy on antibiotic treatment duration based on stopping treatment when stability criteria are reached after at least 48 h of treatment, is non-inferior to the efficacy of standard antibiotic duration in CAP patients treated in the hospital setting.
As the secondary objectives, the study aims
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To study if the efficacy of our experimental strategy on antibiotic treatment duration compared to standard of care in CAP patients treated in the hospital setting is non-inferior in terms of:
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Persistence of cure at Day 30 of antibiotic treatment
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All-cause mortality rate on Day 30 of antibiotic treatment
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Patients evolution of pneumonia symptoms and quality of life via 2 scores (CAP score, CAP Sym) at Day 0 of treatment (retrospectively), at stability (Day S), at Day 7 , at Day 15, and at Day 30 of antibiotic treatment.
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To compare between the 2 study arms at Day 30 of antibiotic treatment:
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The duration of antibiotic treatment;
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The length of hospital stay;
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The frequency and severity of adverse events during the 30 days after the start of treatment.
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To explore the impact of reduced antibiotic treatment duration for CAP on the oropharyngeal resistome.
详细描述
Recent studies have suggested that community-acquired pneumonia (CAP) can be successfully treated with short-course antibiotic regimen when clinical improvement is rapidly obtained. Even if clinical response is obtained in 3 days in the majority of cases, it can vary widely among patients suggesting "one duration does not fit all". An individualised duration of therapy depending on the patient's response could help to ensure bacterial eradication while avoiding unnecessary antibiotic exposure and thus reduce antibiotic resistance. At present, this strategy has never been tested.
This is a phase III, pragmatic, non-inferiority randomised (1:1) national multicentre trial. Population of study participants will be patients admitted to hospital with suspected CAP and in need for antibiotics.
There is no need to establish a DSMB for this trial. The antibiotic treatments prescribed during this study are treatments used in current practice, with well-known adverse drug reactions. Furthermore, a 3-day treatment duration has already been studied in 2 previous randomized clinical trials, showing its safety for hospitalized CAP.
Statistical analysis:
Statistical inference for non-inferiority will be based on the confidence intervals (CI) of the difference in Day 15 cure proportions [proportion in reference arm - proportion in experimental arm] accounting for randomisation stratification factors (centre and delay from Day 0 to Day S (≤ 3 days or > 3 days).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult patient (≥18 years old)
- •Admitted to hospital for suspected CAP defined by the presence of at least 2 of the following diagnostic clinical criteria:
- •Fever (temperature > 38°C) or hypothermia (< 36°C)
- •Production of purulent sputum
- •Radiological evidence of a new infiltrate (chest X-ray or CT scan)
- •Negative viral respiratory testing
- •Treated for a minimum of 48 hours with antibiotics (excluding azithromycin due to its prolonged half-life)Presenting with an early clinical response within the last 24 hours (up to 7 days after the start of antibiotic treatment, if planned treatment duration > 7 days), defined by the presence of all the following criteria:apyrexia (T°C ≤ 37.8)heart rate < 100/minrespiratory rate < 24/min, according to the patient's usual mode of oxygenation,arterial oxygen saturation ≥ 92%, according to the patient's usual mode of oxygenation,Patient currently under antibiotic treatment for his suspected CAP (i.e. the last dose of ATB has been administered to the patient less than 24 hours ago)
- •Patient presenting a clinical response within the last 24 hours defined by the presence of all the following criteria:
- •apyrexia (T°C ≤ 37.8)
- •heart rate < 100/min
- •respiratory rate < 24/min, according to the patient's usual mode of oxygenation,
- •arterial oxygen saturation ≥ 92%, according to the patient's usual mode of oxygenation,
- •systolic blood pressure ≥ 90mmHg, The last occurring of these criteria must have appeared within the last 24 hours.
- •The antibiotic treatment for suspected CAP has started at least 48 hours ago and at most 6 days ago
- •No other site of infection besides respiratory
- •Affiliated to Health insurance
- •Has given informed consent
- •Patient understanding oral and written French, or presence of a relative who can explain and help him complete the study documents
排除标准
- •Signs of severe CAP (abscess, massive pleural effusion, serious chronic respiratory insufficiency)
- •Known immunosuppression (asplenia, neutropenia, agammaglobulinemia, transplant, myeloma, lymphoma, known HIV and CD4<200/mm3)
- •Suspected or confirmed legionellosis
- •Any other infection necessitating concomitant antibiotic treatment
- •Confirmed or suspected aspiration pneumonia or healthcare-associated pneumonia
- •Treatment of suspected CAP with azithromycin (due to its prolonged half-life)
- •Concomitant steroid treatment (only for patients treated with fluoroquinolones antibiotics)
- •Pre-existing aortic aneurysm or dissection, family history of aortic aneurysm or dissection, Marfan syndrome, Ehlers-Danlos syndrome, Takayasu arthritis, uncontrolled arterial hypertension, atherosclerosis (only for patients treated with fluoroquinolones antibiotics)
- •Pregnant or breastfeeding woman
- •Life expectancy < 1 month
- •Patient under legal guardianship (French "tutelle" or "curatelle")
- •Patient without fixed address
- •Patient enrolled in another interventional clinical trial on CAP treatment
研究组 & 干预措施
Antibiotic treatment
Antibiotic treatment duration left to the physician's judgment (usual practice: total treatment duration between 5 to 10 days according to French guidelines; more than 7 days of treatment should be justified).
干预措施: Continue the antimicrobial treatment (Drug)
Interruption of treatment
Interruption of treatment based on the patient reaching all of the following stability criteria (body temperature ≤ 37.8°C; heart rate ≤ 100/min; systolic blood pressure > 90mmHg; oxygen saturation ≥ 92%; respiratory rate < 24/min; normal mental status (27)), with a treatment duration no shorter than 48 h.
干预措施: Stop antibiotic (Other)
结局指标
主要结局
Rate of cure at Day 15 after treatment initiation
时间窗: Day 15
Cure at Day 15 will be defined by the association of: * Persistence of stability criteria (body temperature ≤ 37.8°C; heart rate ≤ 100/min; systolic blood pressure \> 90mmHg; oxygen saturation ≥ 92%; respiratory rate \< 24/min; normal mental status); * No additional antibiotic treatment, targeting CAP, taken after the end of initial antibiotic treatment. Patients who died, or are not cured as defined above, will be classified as failure at Day 15.
次要结局
- Mortality on Day 30(Day 30)
- Patients' evolution of pneumonia symptoms(Day 15 and Day 30)
- Duration of antibiotic treatment targeting CAP(Day 30)
- Rate of cure at Day 30(Day 30)
- Duration of antibiotic treatment for all indications(Day 30)
- Length of hospitalization(Day 30)
- Incidence of adverse event(Day 30)
- Number of resistance genes(Day S and Day 30)